PB2178: OUTCOMES OF REDUCED DOSE TEAM (THIOTEPA, ETOPOSIDE, CYTARABINE, MELPHALAN) PRIOR TO AUTOLOGOUS STEM CELL TRANSPLANTATION FOR HODGKIN AND NON-HODGKIN LYMPHOMA: A MONOCENTRIC EXPERIENCE
Authors: S. Di Folca, V. Marafioti, S. barbato, S. Avilia, F. Grimaldi, A. Severino, M. Picardi, L. Luciano, G. Battipaglia, F. Pane
Journal: HemaSphere (2022)

Background: Combination of carmustine, etoposide, cytarabine, melphalan (BEAM) is a commonly used regimen for autologous stem cell transplantation (auto-SCT) in patients with Hodgkin (HL) or non-Hodgkin lymphoma. Due to both a shortage of carmustine in the past decade and to reduce its pulmonary toxicity, this agent has been replaced in several centers by thiotepa (TEAM). However, BEAM and TEAM are associated with mucosal toxicities. Therefore, in our center since 2015 we reduced cytarabine and etoposide doses to reduce conditioning toxicities. Aims: Study is designed to explore whether halving the doses of cytarabine and etoposide can reduce transplant-related toxicity while maintaining the antitumor response. Methods: We retrospectively analyzed transplant outcomes of adult patients undergoing auto-SCT conditioned with reduced TEAM (thiotepa 5mg/kg/12h on day -7; etoposide 100 mg/m2/12h and cytarabine 100 mg/m2/12h on days -6 to -3 (instead of the commonly used 200 mg/m2/12h); melphalan 140 mg/m2 on day -1). Results: Included were thirty-nine patients (males, n=24; females, n=15) transplanted during the period 2015-2021. Median age was 43 (range 22-65) years. Most patients were transplanted for refractory (n=10) or relapsed (n=15) disease, while 12 patients were transplanted after first line treatment. The most frequent histology was diffuse large B-cell lymphoma (n= 15) followed by HL (n=10), follicular lymphoma (n=5), mantle cell lymphoma (n= 5) and primary mediastinal B-cell lymphoma (n=4). The median number of chemotherapy lines prior to transplant was 2 (range 1-5), with a median interval from diagnosis to transplant of 16 months (range 5-218). Disease status at auto-SCT was complete response (CR) in 37 (CR1=22, CR2=14, >CR2=1) and partial response (PR) in 2 patients. Eight patients needed plerixafor for CD34 mobilization, with a median dose of CD34+ collected of 3.36 (range 0.70-17.00) x 106 /kg. All but 1 patient engrafted, with a median time to neutrophil and platelet engraftment of 11 (range 8-16) and 19 (range 9-40) days, respectively. The median duration of hospitalization was 19 days (range 15-27). Regimen related toxicities included mucositis in 32 patients (82%; grade 1-2, n=29; grade 3, n=3; no grade 4 mucositis) and febrile neutropenia in 26 patients (67%). Blood cultures were positive for Gram-positive or Gram-negative bacteria in 3 and 8 patients, respectively. One patient developed resolutive pneumonia. Five patients (13%) underwent maintenance therapy after transplantation (brentuximab, n=3; rituximab, n=1; ibrutinib, n=1) while twelve patients relapsed with a median time after auto-SCT of 5.5 (range 3-19) months, with a 1-year cumulative incidence of relapse of 38% [95% CI 20-56]. Two patients underwent allogeneic SCT with a median time after auto-SCT of 11 and 23 months, respectively. The 100-day and one-year non-relapse-mortality (NRM) was 2.5% [95% CI 0.2-11]. Eight patients died: one 5 days after auto-SCT due to septic shock; 5 due to disease progression and 2, after disease relapse, due to suicide and cerebral hemorrhage, respectively. At last follow-up, 29 patients (81%) were in CR. With a median follow-up of 21 (range3-77) months, 2-year progression-free and overall survival were 59%[95% CI 38-75] and 81% [95% CI 74-88]. Median PFS was 14 months (range 0-77) and median OS was 17 months (range 0-77). Summary/Conclusion: Reduced TEAM is a feasible and valid regimen prior to auto-SCT, with low toxicity and NRM and acceptable survival rates.